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An emerging method to noninvasively measure and identify vagal response markers to enable bioelectronic control of gastroparesis symptoms with gastric electrical stimulation
Abstract
Background:
Gastric electrical stimulation (GES) can be a life-changing, device-based treatment option for drug-resistant nausea and vomiting associated with diabetic or idiopathic gastroparesis (GP). Despite over two decades of clinical use, the mechanism of action remains unclear. We hypothesize a vagal mechanism.
New method:
Here, we describe a noninvasive method to investigate vagal nerve involvement in GES therapy in 66 human subjects through the compound nerve action potential (CNAP).
Results:
Of the 66 subjects, 28 had diabetic GP, 35 had idiopathic GP, and 3 had postsurgical GP. Stimulus charge per pulse did not predict treatment efficacy, but did predict a significant increase in total symptom score in type 1 diabetics as GES stimulus charge per pulse increased (p < 0.01), representing a notable side effect and providing a method to identify it. In contrast, the number of significant left and right vagal fiber responses that were recorded directly related to patient symptom improvement. Increased vagal responses correlated with significant decreases in total symptom score (p < 0.05).
Comparison with existing method(s):
We have developed transcutaneous recording of cervical vagal activity that is synchronized with GES in conscious human subjects, along with methods of discriminating the activity of different nerve fiber groups with respect to conduction speed and treatment response.
Conclusions:
Cutaneous vagal CNAP analysis is a useful technique to unmask relationships among GES parameters, vagal recruitment, efficacy and side-effect management. Our results suggest that CNAP-guided GES optimization will provide the most benefit to patients with idiopathic and type 1 diabetic gastroparesis.
... Contributing factors include suboptimal neural interface design, lack of stimulus specificity, and a 'one size fits all' approach to clinical neuromodulation. Computational modelling has been important for accelerating the design of neural interfaces (Sperry et al., 2018;Romeni et al., 2020;Ward et al., 2020a;Larson and Meng, 2020;Leventhal and Durand, 2003), improving our understanding of stimulus specificity (Bucksot et al., 2021;Leventhal and Durand, 2003;Romeni et al., 2020), and understanding how subject-specific variation in nerve anatomy affects peripheral nerve stimulation (Grinberg et al., 2008;Musselman et al., 2021;Pelot et al., 2019). Accordingly, many computational models have been used to study neural interfaces for delivering neuromodulation (e.g. ...
... In order to help patients engage in dynamic behaviors such as micturition (Payne et al., 2020), the efficacy of neural interfaces applied to visceral nerves may be improved by recording neural activity to control delivery of neuromodulation (Bouton and Czura, 2018;Larson and Meng, 2020). An example of such an approach is closed-loop control by monitoring electrically-evoked compound actions potentials (ECAPs) for self-calibration of stimulation parameters, an approach which has been applied extensively in cochlear interfaces (DeVries et al., 2016), the vagus nerve (Ward et al., 2015(Ward et al., , 2020a and spinal cord stimulation (Parker et al., 2017). However, in comparison to the many models of neuromodulation, far fewer models have addressed the problem of optimizing neural recording performance (Struijk, 1997;Karimi and Seydnejad, 2015;Lubba et al., 2019;Smets et al., 2021;Buccino and Einevoll, 2021). ...
Objective:
Neuromodulation of visceral nerves is being intensively studied for treating a wide range of conditions, but effective translation requires increasing the efficacy and predictability of neural interface performance. Here we use computational models of rat visceral nerve to predict how neuroanatomical variability could affect both electrical stimulation and recording with an experimental planar neural interface.
Approach:
We developed a hybrid computational pipeline, Visceral Nerve Ensemble Recording & Stimulation (ViNERS), to couple finite-element modelling of extracellular electrical fields with biophysical simulations of individual axons. Anatomical properties of fascicles and axons in rat pelvic and vagus nerves were measured or obtained from public datasets. To validate ViNERS, we simulated pelvic nerve stimulation and recording with an experimental four-electrode planar array.
Main results:
Axon diameters measured from pelvic nerve were used to model a population of myelinated and unmyelinated axons and simulate recordings of electrically evoked single-unit field potentials (SUFPs). Across visceral nerve fascicles of increasing size, our simulations predicted an increase in stimulation threshold and a decrease in SUFP amplitude. Simulated threshold changes were dominated by changes in perineurium thickness, which correlates with fascicle diameter. We also demonstrated that ViNERS could simulate recordings of electrically-evoked compound action potentials (ECAPs) that were qualitatively similar to pelvic nerve recording made with the array used for simulation.
Significance:
We introduce ViNERS as a new open-source computational tool for modelling large-scale stimulation and recording from visceral nerves. ViNERS predicts how neuroanatomical variation in rat pelvic nerve affects stimulation and recording with an experimental planar electrode array. We show ViNERS can simulate ECAPS that capture features of our recordings, but our results suggest the underlying NEURON models need to be further refined and specifically adapted to accurately simulate visceral nerve axons.
... Reliable interfacing of flexible, stretchable, and soft electronics with the human body could advance a wide range of medical technologies such as chronic braincomputer interfaces, [1][2][3][4][5][6] implantable electrophysiological sensors, [7][8][9][10] active drug delivery systems, [11][12][13][14][15][16] wearable health monitoring devices, [17][18][19][20][21][22][23][24] and electrical stimulatory therapeutic devices. [25][26][27][28][29][30][31][32][33] Electronic devices with flexible and compliant form factors permit con formal integration with tissues in the human body, which are often soft, curvilinear, and dynamic. [34][35][36] While the prospects for biomedical applications are promising, transforming flex ible electronics from laboratory curiosities into robust and reli able medical devices creates new challenges in fabrication and deployment. ...
Designing bioelectronic devices that seamlessly integrate with the human body is a technological pursuit of great importance. Bioelectronic medical devices that reliably and chronically interface with the body can advance neuroscience, health monitoring, diagnostics, and therapeutics. Recent major efforts focus on investigating strategies to fabricate flexible, stretchable, and soft electronic devices, and advances in materials chemistry have emerged as fundamental to the creation of the next generation of bioelectronics. In this review, the summarize contemporary advances and forthcoming technical challenges related to three principal components of bioelectronic devices: (i) substrates and structural materials, (ii) barrier and encapsulation materials, and (iii) conductive materials. Through notable illustrations from the literature, integration and device fabrication strategies and associated challenges for each material class are highlighted.
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... Vagal nerve stimulation has been shown to offer therapeutic benefit for modulating gastric function (see section "Electrical Conduction System of the Stomach") (Payne et al., 2019;Ward et al., 2020). However, mathematical models of the enteric nervous system have largely focused on interaction with the small intestine (Chambers et al., 2014;O'Sullivan-Greene et al., 2018). ...
Gastric pacing and stimulation strategies were first proposed in the 1960s to treat motility disorders. However, there has been relatively limited clinical translation of these techniques. Experimental investigations have been critical in advancing our understanding of the control mechanisms that innervate gut function. In this review, we will discuss the use of pacing to modulate the rhythmic slow wave conduction patterns generated by interstitial cells of Cajal in the gastric musculature. In addition, the use of gastric high-frequency stimulation methods that target nerves in the stomach to either inhibit or enhance stomach function will be discussed. Pacing and stimulation protocols to modulate gastric activity, effective parameters and limitations in the existing studies are summarized. Mathematical models are useful to understand complex and dynamic systems. A review of existing mathematical models and techniques that aim to help refine pacing and stimulation protocols are provided. Finally, some future directions and challenges that should be investigated are discussed.
... We hope by publishing this Special Issue to draw attention to these incredible discoveries of the past few years and to collect in one place a series of best practice recommendations as a valuable resource for PNI researchers. Among the compiled reports are key insights on surgical techniques (Dingle et al., 2019), on mapping fascicular connections (Thompson et al., 2019), on identifying dorsal horn neurons (Smith et al., 2020), on blocking mammalian motor nerves (Bhadra et al., 2020), and evaluating vagal nerve involvement in gastric stimulation (Ward et al., 2020). In addition, invited authors present comprehensive reviews on somatic neuroprostheses (Raspopovic et al., 2020) and PNI design , as well as guides on clinical translation (Charkhkar et al., 2019) and assessment of chronic PNI safety (Shafer et al., 2019). ...
Key points:
It has previously been shown that afferent and efferent vagal nerve stimulation potently inhibits LPS-induced inflammation Our data show inhibition of inflammation by efferent but not afferent vagal nerve stimulation requires T-cell derived acetylcholine We show that afferent and efferent neuroimmune circuits require β2 -adrenergic receptor signaling ABSTRACT: Chronic inflammation due to inappropriate immune cell activation can have significant effects on a variety of organ systems, reducing lifespan and quality of life. As such, highly targeted control of immune cell activation is a major therapeutic goal. Vagus nerve stimulation (VNS) has emerged as a therapeutic modality that exploits neuro-immune communication to reduce immune cell activation and consequently inflammation. Although vagal efferent fibers were originally identified as the primary driver of anti-inflammatory actions, the vagus nerve in most species of animals is predominantly comprised of afferent fibers. Stimulation of vagal afferent fibers can also reduce inflammation; it is however uncertain how these two neuro-immune circuits diverge. Here we show that afferent VNS induces a distinct mechanism from efferent VNS, ameliorating LPS-induced inflammation independent from T-cell derived acetylcholine (ACh) that is required by efferent VNS. Using a β2 -adrenergic receptor antagonist (β2 -AR), we find that immune regulation induced by intact, afferent, or efferent VNS occur in a β2- AR-dependent manner. Together, our findings indicate that intact VNS activates at least two distinct neuroimmune circuits each with unique mechanisms of action. Selective targeting of either the vagal efferent or afferent fibers may provide more personalized, robust, and effective control over inappropriate immune responses. This article is protected by copyright. All rights reserved.
The gastrointestinal tract has extensive, surgically accessible nerve connections with the central nervous system. This provides the opportunity to exploit rapidly advancing methods of nerve stimulation to treat gastrointestinal disorders. Bioelectric neuromodulation technology has considerably advanced in the past decade, but sacral nerve stimulation for faecal incontinence currently remains the only neuromodulation protocol in general use for a gastrointestinal disorder. Treatment of other conditions, such as IBD, obesity, nausea and gastroparesis, has had variable success. That nerves modulate inflammation in the intestine is well established, but the anti-inflammatory effects of vagal nerve stimulation have only recently been discovered, and positive effects of this approach were seen in only some patients with Crohn’s disease in a single trial. Pulses of high-frequency current applied to the vagus nerve have been used to block signalling from the stomach to the brain to reduce appetite with variable outcomes. Bioelectric neuromodulation has also been investigated for postoperative ileus, gastroparesis symptoms and constipation in animal models and some clinical trials. The clinical success of this bioelectric neuromodulation therapy might be enhanced through better knowledge of the targeted nerve pathways and their physiological and pathophysiological roles, optimizing stimulation protocols and determining which patients benefit most from this therapy.
This study determined the most efficient parameters of low-frequency/long-pulse gastric electrical stimulation (GES) required to entrain gastric slow waves and also evaluated the effect of entrainment and high-frequency, short-pulse GES on gastric electrical activity (GEA). Nine dogs were fitted with stimulation wires along the greater curvature. Entrainment was observed in six or seven animals, with long-pulse GES at six cycles per minute (cpm), at various combinations of current and pulse width and was directly related to the energy delivered. Entrainment was observed in four to seven animals, with GES at 12 cpm, and the maximal driven frequency was 6 cpm. Entrainment did not significantly increase the dominant power of GEA. High-frequency, short-pulse GES, using pulse trains of 14 Hz, 5 mA, and 330 micros, with 0.1 s on and 5 s off, and pulse trains of 40 Hz, 10 mA, and 330 micros, with 2 s on 3 s off, did not affect variables of GEA. We conclude that acute low-frequency GES but not high-frequency, short-pulse GES can entrain slow waves; the power of slow waves is not affected by either type of stimulation.
The treatment of gastroparesis remains unsatisfactory despite prokinetic and anti-emetic drugs. Gastric electrical stimulation has been proposed as a therapeutic option. We have assessed the effect of gastric electrical stimulation on symptoms, medical treatment, body weight and gastric emptying in patients with intractable symptomatic gastroparesis in a non-placebo-controlled study.
In this multicenter study, 38 highly symptomatic patients with drug-refractory gastroparesis were enrolled. Patients first received temporary electrical stimulation using percutaneous electrodes. The 33 responders to temporary stimulation then underwent surgical implantation of a permanent stimulator. Severity of vomiting and nausea was assessed before and after stimulation. Patients were reassessed 3, 6, and 12 months after permanent implantation.
With stimulation, 35/38 patients (97%) experienced >80% reduction in vomiting and nausea. This effect persisted throughout the observation period (2.9-15.6 months, 341 patient-months). Gastric emptying did not initially change, but improved in most patients at 12 months. At 1 year, the average weight gain was 5.5% and 9/14 patients initially receiving enteral or parenteral nutrition were able to discontinue it.
Electrical stimulation of the stomach has an immediate and potent anti-emetic effect. It offers a safe and effective alternative for patients with intractable symptomatic gastroparesis.
As more is learned about the mechanism of operation of the central nervous system, the characteristic of the mechanism that becomes the most impressive is the exquisite timing of the events. For example, if an impulse of subliminal effectiveness impinges upon a synapse, it leaves a trace which lasts only a few tenths of a millisecond. If within that time another impulse, likewise of subliminal effectiveness, arrives at the same region on the surface of the neuron, the two impulses together will raise excitation to the threshold, and a relayed message will be sent upon its way. Stated in other words, if the two impulses arrive at the synapse at an interval of separation longer than a few tenths of a millisecond, there is no transmission; and the local disturbance that each impulse produces dies out promptly, to leave the junctional area restored to its antecedent state ready for any new impulses that may be coming on. Transmission at any point thus depends upon the arrival of excitation from the various controlling centers in exactly the right time relations. Thereby the flow of impulses is always properly directed toward the end reaction appropriate to the conditioning data picked up by the body receptors. The timing of impulses starts in the beginning of all reactions—in the sensory messages that report changes in the state of the body and in the character of the environment. At least no other interpretation explains as satisfactorily why sensory messages are carried at so wide a range of velocities. For some reason not at all well understood it is necessary for some impulses to shoot out ahead to prepare the central nervous system for other impulses that arrive later. In as simple an event as pricking the skin of the finger with a needle there is first a short burst of impulses carried in fibers conducting at 90 meters or more per second (20). Then there follow impulses at other velocities, many at about twenty meters per second; and finally there is a trail of impulses at about one meter per second. Before any of the last mentioned group arrives at the centers, a complex neurological event has taken place— the withdrawal of the hand; and the sensation of pricking has been appreciated. The sensation aroused by the slow fibers is still, however, that of pain indistinguishable qualitatively from the pain already felt. But in its setting it has a stinging, irritating character. It can be relieved by rubbing the spot, that is, it may be inhibited by sending into the central nervous system a flood of impulses carried in rapidly conducting fibers. It is not my intention in the present paper to follow up this argu-ment, but to let the observations stand as an introductory background to the main theme, which is the basis of the numerous velocities in nerve fibers. Visualization of the wide range of velocities can best be accom-145 146 HERBERT S. GASSER Vol. XLI plished by showing what happens when a sensory nerve is artificially stimulated with an electrical shock of short duration. All the impulses start out together from the locus of the stimulus, but the fast impulses forge ahead. Thus, if a lead be taken at some distance from the point of stimulation, at the beginning of the action potential there are initially recorded the first impulses to arrive; and the other impulses are recorded later, at times inversely proportional to their velocities. As all the velocities are not equally represented among the fibers, the result is an action potential with distinctive elevations. The contour here pre-sented (Pig. 1), taken from the saphenous nerve of the cat, is character-istic of all sensory nerves. It starts with a high elevation contributed by fibers conducting at velocities ranging approximately between 95 and 35 m.p.s. The high elevation is succeeded by a very small one in which velocities between 35 and 22 m.p.s. are represented; and this in turn is followed by a somewhat larger one representing velocities between 22 and 15 m.p.s. In the wake of the latter there are still a few impulses at a velocity slower than 15 m.p.s. Figure 1 (left). Action potential of the saphenous nerve of the cat as recorded after 4 cm. of conduction from the stimulating cathode. The first disturbance in the line marks the moment of stimulation, and the interval between this point and the start of the first high elevation measures the conduction time of the fastest fibers. The potentials contributed by the other fibers follow in succession. Figure 2 (right). Action potential of the saphenous nerve of the rabbit as recorded after 4 cm. of conduction.
Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus but its actions are not well defined in musk shrews, a primary small animal model used to study emesis. The aims of the current study were (1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and (2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg, ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg, sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggests brainstem anatomical circuits that are activated by GI signaling in the musk shrew.
Electrical stimulation, or pacing of the stomach has been advocated as a possible treatment for gastric motor dysfunction (1± 11). The rationale stems from the important role played by the electrical control activity (ECA) component of gastric electrical activity (GEA). To date, researchers have employed frequencies similar to, or slightly higher than the native ECA frequency in gastric stimulation (1± 11). In another study, we demonstrated a comparative superiority of high-frequency (ie, several times the basal rate) gastric electrical stimulation (GES) over low-frequency (similar to the basal rate) stimulation in the canine stomach (12). In that study, GES at 20 cycles/min elicited the largest motility index in canine stomach of all the frequencies tested. Compared with the nominal canine ECA frequency of 5 cycles/min, this implies a frequency of approximately four times the physiologic rate. In the present study, we elected a similar higher than physiologic frequency signal to investigate the ef® cacy of GES in improving gastric emptying and symptoms in a patient with refractory diabetic gastroparesis. We chose a pacing signal of 12 cycles/min, approximately four times the nominal physiologic frequency of 3 cycles/min in the human stomach.
Recent evidence of the significant impact of gastroparesis on morbidity and mortality mandates optimized management of this condition. Gastroparesis affects nutritional state, and in diabetics it has deleterious effects on glycemic control and secondary effects on organs that increase mortality. First-line treatments include restoration of nutrition and medications (prokinetic and antiemetic). We review the epidemiology, pathophysiology, impact, natural history, time trends, and treatment of gastroparesis, focusing on diabetic gastroparesis. We discuss pros and cons of current treatment options, including metoclopramide. Second-line therapeutic approaches include surgery, venting gastrostomy or jejunostomy, and gastric electrical stimulation; most of these were developed based on results from open-label trials. New therapeutic strategies for gastroparesis include drugs that target the underlying defects, prokinetic agents such as 5-hydroxytryptamine agonists that do not appear to have cardiac or vascular effects, ghrelin agonists, approaches to pace the stomach, and stem cell therapies.
We investigated the effects of electrical stimulation of the stomach on gastric emptying and the electrical activity of the stomach in 10 dogs. A model of gastroparesis was developed in five dogs using truncal vagotomy combined with injections of glucagon. Glucagon also induced electrical dysrhythmias. Bipolar electrodes were implanted in the stomach and the duodenum for electrical stimulation and for recording electrogastrograms. Gastric emptying of an isotope-labeled solid meal was assessed for 2 h. External electrical stimulation was delivered to the corpus of the stomach at its own physiological frequency to investigate whether it could restore normal gastric emptying. Such stimulation had no significant effect on gastric emptying in intact animals (45 vs. 43%: retention of isotope after 2 h) or when only vagotomy was performed (78 vs. 66%), but it significantly accelerated gastric emptying in animals with vagotomy and glucagon (from 86 to 68%). From this model of delayed gastric emptying, we suggest that electrical stimulation of the stomach at its own intrinsic frequency may recoordinate uncoupled slow wave activity induced by glucagon after vagotomy thus improving the rate of gastric emptying.
Gastric pacing has been achieved in dogs and humans, but its effects on gastric motility and emptying have not been thoroughly explored. Seven dogs had bipolar electrodes placed 1 and 10 cm proximal to the pylorus for reverse and forward pacing and monopolar recording electrodes and strain gauges placed 3, 5, and 7 cm proximal to the pylorus. After recovery, myoelectrical and contractile activity and gastric emptying of a mixed meal (50 g 99mTc-labeled liver and 250 ml 111In-labeled 5% dextrose broth solution) were measured in each of three conditions: no pacing, reverse pacing, and forward pacing (frequency 0.5 cycles/min above intrinsic pacesetter potential frequency). Reverse pacing reversed the direction of > 90% of antral pacesetter potentials and peristaltic waves in six of seven dogs, prolonged the lag phase of solid emptying, prolonged the half emptying time of solids and liquids, and increased the antral motility index. Forward pacing entrained pacesetter potentials but had no consistent effect on emptying or antral contractions. In conclusion, reverse gastric pacing slows gastric emptying of digestible solids and liquids by reversing the direction of antral peristalsis and increasing the antral motility index, whereas forward pacing has no such effects.
The optimum frequency for electrically stimulating motility in the stomach is still in question. Some studies of gastric electrical stimulation (GES) at near physiologic frequencies have reported gastric electrical entrainment but with little efficacy in improving motility. In this study we examined the effectiveness of electrical stimulation at a broad range of frequencies in entraining gastric electrical activity (GEA) and eliciting contractions in a canine model. The stomachs of six dogs, each implanted with four pairs of stainless steel electrodes and two strain gauges were stimulated at frequencies ranging from 3 to 30 cycles/min. GEA and contractions were monitored before and during electrical stimulation. The ability of GES at different frequencies to reverse the effect of glucagon was also investigated. GEA was entrained in most animals at frequencies close to the intrinsic rate as well as at four to five times the intrinsic rate. At other stimulation frequencies, the recorded electrical control activity either remained unchanged, uncoupled, or became dysrhythmic. Contractile response to stimulation at four to five times the intrinsic rate were significantly higher than those at frequencies close to the intrinsic rate (P < 0.05). GES did not alter the effect of glucagon. Stimulation at a frequency of four times the basal rate of 5/min elicited the largest motility index in dogs. Stimulation at frequencies much higher than the physiologic rate warrants further study as a possible optimum range for GES.
The aim of this study was to investigate the effect of pacing parameters on the entrainment of gastric slow waves in patients with gastroparesis. Four pairs of cardiac pacing wires were placed on the serosal surface of the stomach in 13 patients with gastroparesis. After a baseline recording for 30 min, gastric pacing was performed in a number of sessions with different effective parameters, each lasting for 30 min. The following parameters were found to be effective for the entrainment of the gastric slow wave: a pacing frequency 10% higher than the intrinsic gastric slow wave frequency (IGF), 300 ms pulse width, and 4 mA pacing amplitude. A reduction of pacing amplitude from 4 to 2 mA and 1 mA reduced the percentage of entrainment of the gastric slow wave to 79 +/- 10% and 50 +/- 11%, respectively. Pacing with a pulse width of 30 or 3 ms was not able to entrain the gastric slow wave in any of the patients. An ectopic pacemaker of tachygastria found in three patients was reversed with gastric pacing. It was concluded that gastric pacing at a frequency up to 10% higher than the IGF and with an amplitude of 4 mA and a pulse width of 300 ms is able to completely entrain the gastric slow wave and normalize gastric dysrhythmias in patients with gastroparesis.
No effective treatment is available for patients with gastroparesis refractory to standard medical therapy. The aim of this study was to investigate the effects of gastric pacing on gastric electrical activity, gastric emptying, and symptoms in patients with gastroparesis.
Nine patients with gastroparesis participated in this study. Four pairs of cardiac pacing wires were implanted on the serosa of the stomach. The protocol consisted of two portions: a temporary inpatient study period and an outpatient study for a period of 1 month or more.
Gastric pacing entrained the gastric slow wave in all subjects and converted tachygastria in 2 patients into regular 3-cpm slow waves. Gastric emptying was significantly improved after the outpatient treatment with gastric pacing. The gastric retention at 2 hours was reduced from 77.0% +/- 3.3% to 56.6% +/- 8.6% (P < 0.05). Symptoms of gastroparesis were substantially reduced at the end of the outpatient treatment (1.51 +/- 0.46 vs. 2.84 +/- 0.61; P < 0.04). Eight of 9 patients no longer relied on jejunostomy tube feeding, and no adverse events were noted related to the pacing unit.
Gastric pacing seems to be able to improve symptoms of gastroparesis and to accelerate gastric emptying in patients with gastroparesis. More controlled studies are necessary to further investigate the role of gastric pacing in clinical practice.
Patients with gastroparesis frequently present challenging clinical, diagnostic, and therapeutic problems. Data from 146 gastroparesis patients seen over six years were analyzed. Patients were evaluated at the time of initial diagnosis and at the most recent follow-up in terms of gastric emptying and gastrointestinal symptomatology. The psychological status and physical and sexual abuse history in female idiopathic gastroparesis patients were ascertained and an association between those factors and gastrointestinal symptomatology was sought. Eighty-two percent of patients were females (mean age: 45 years old). The mean age for onset of gastroparesis was 33.7 years. The etiologies in 146 patients are: 36% idiopathic, 29% diabetic, 13% postgastric surgery, 7.5% Parkinson's disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudoobstruction, and 6% miscellaneous causes. Subgroups were identified within the idiopathic group: 12 patients (23%) had a presentation consistent with a viral etiology, 48% had very prominent abdominal pain. Other subgroups were gastroesophageal reflux disease and nonulcer dyspepsia (19%), depression (23%), and onset of symptoms immediately after cholecystectomy (8%). Sixty-two percent of women with idiopathic gastroparesis reported a history of physical or sexual abuse, and physical abuse was significantly associated with abdominal pain, somatization, depression, and lifetime surgeries. At the end of the follow-up period, 74% required continuous prokinetic therapy, 22% were able to stop prokinetics, 5% had undergone gastrectomy, 6.2% went onto gastric electrical stimulation (pacing), and 7% had died. At some point 21% had required nutrition support with a feeding jejunostomy tube or periods of parenteral nutrition. A good response to pharmacological agents can be expected in the viral and dyspeptic subgroups of idiopathics, Parkinson's disease, and the majority of diabetics, whereas a poorer outcome to prokinetics can be expected in postgastrectomy patients, those with connective tissue disease, a subgroup of diabetics, and the subset of idiopathic gastroparesis dominated by abdominal pain and history of physical and sexual abuse. Appreciation of the different etiologies and psychological status of the patients may help predict response to prokinetic therapy.
Patient-based symptom assessments are necessary to evaluate the effectiveness of medical treatments for gastroparesis.
To summarize the development and measurement qualities of the Gastroparesis Cardinal Symptom Index (GCSI), a new measure of gastroparesis-related symptoms.
The GCSI was based on reviews of the medical literature, clinician interviews and patient focus groups. The measurement qualities (i.e. reliability, validity) of the GCSI were examined in 169 gastroparesis patients. Patients were recruited from seven clinical centres in the USA to participate in this observational study. Patients completed the GCSI, SF-36 Health Survey and disability day questions at a baseline visit and again after 8 weeks. Clinicians independently rated the severity of the patients' symptoms, and both clinicians and patients rated the change in gastroparesis-related symptoms over the 8-week study.
The GCSI consists of three sub-scales: post-prandial fullness/early satiety, nausea/vomiting and bloating. The internal consistency reliability was 0.84 and the test-re-test reliability was 0.76 for the GCSI total score. Significant relationships were observed between the clinician-assessed symptom severity and the GCSI total score, and significant associations were found between the GCSI scores and SF-36 physical and mental component summary scores and restricted activity and bed disability days. Patients with greater symptom severity, as rated by clinicians, reported greater symptom severity on the GCSI. The GCSI total scores were responsive to changes in overall gastroparesis symptoms as assessed by clinicians (P = 0.0002) and patients (P = 0.002).
The findings of this study indicate that the GCSI is a reliable and valid instrument for measuring the symptom severity in patients with gastroparesis.